Long-term respiratory support using endotracheal intubation and positive pressure ventilation is associated with very high rates of infection, and ventilator-associated pneumonia (VAP) is among the leading and more serious forms of nosocomial infection in hospitals today. The objective of this program is the development of a new negative pressure ventilator that eliminates indwelling components and allows the patient to breathe room air to reduce the incidence of VAP. The prototype negative pressure ventilator is the "iron lung" originally developed by Drinker in 1929. It essentially consisted of a metal tank containing the patient's entire body up to the neck. The pressure inside the tank was cycled below ambient pressure to induce inhalation, and then returned to ambient to allow exhalation. That device was used successfully to support many patients for extended periods during the polio epidemics in the late 1950s, but it was large, greatly limited access to the patient for routine nursing care, and provided a very limited quality of life. We are proposing to build and test prototypes of a new negative pressure ventilator that is small and light in weight. The principle of operation is the similar to the iron lung, but instead of a tank, it employs a two-segment artificial rib cage assembly with an elastomeric jacket closely surrounding the chest wall. The artificial rib cage is mechanically actuated to mimic the movement of the chest wall during respiration, creating a negative pressure around the chest and upper abdomen during inhalation. Using a manikin, we have demonstrated that this design is able to generate negative pressures greater than -20 cm of water, enough to induce inhalation in an adult human subject. Because it is mechanically actuated, it may also be used to induce or augment a cough to clear the airways, a unique capability. In the proposed program, we will design and build prototypes of the device and develop an electronic control system that will permit either patient triggered fixed rate operation. We will then characterize its performance with a series of 6 acute in vivo studies using a porcine model. The new device overcomes many of the limitations of existing negative or positive pressure ventilation systems and has the potential to significantly reduce the incidence of VAP. PUBLIC HEALTH RELEVANCE: The objective of this proposal is the development of a novel negative pressure ventilator that will provide respiratory support without endotracheal intubation or the use of a conventional positive pressure ventilator. The latter devices are associated with high rates of infection (>60%) when used for periods exceeding 30 days, and ventilator-associated pneumonia is one of the major classes of nosocomial infection and causes significant morbidity. By introducing no indwelling components into the airway and allowing the patient to breathe room air, the infection rate associated with prolonged respiratory support can be significantly reduced. [unreadable] [unreadable] [unreadable]